Cell plasticity in patients with NSCLC: The controversial origins of transformed SCLC

In recent years, the application of targeted therapy has greatly improved the survival of NSCLC patients with known tumor mutations. However, the plasticity of tumor cells can drive them to transform into a phenotypic state that is no longer targeted by drugs. One of the mechanisms by which drug resistance occurs is the transformation from NSCLC to SCLC. This seems to occur because of the selection pressure exerted by the drugs. However, the transformation has also been observed in non-targeted patients, which challenges the origin of transformed SCLC. In the present study, the current clinical understanding of transformed SCLC is summarized along with the current understanding of its genome status and cloning history in cancer progression. This was done to explore the origins of transformed SCLC, find key molecular markers to predict the occurrence of the transformation, and permit timely adjustment of patients' treatment plans. Besides, the current clinical trials on transformed SCLC are discussed. Finally, recommendations are made on the problems that need to be solved to improve the diagnosis and treatment of patients with transformed SCLC.